title: Pharmacokinetics, pharmacodynamics, and safety of esomeprazole injection/infusion in healthy Chinese volunteers: a five-way crossover study.
abstract: BACKGROUND
  Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the Chinese population remain unclear.
  
  
  OBJECTIVE
  To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy Chinese subjects.
  
  
  METHODS
  A randomized, single-center, open-label, five-way crossover study was conducted in 20 healthy volunteers. CYP2C19 metabolizer genotype and Helicobacter pylori status were examined. Five dosing regimens were used: single 40 mg injection, 40 mg infusion every 12 h, 40 mg infusion followed by continuous infusion at 8 mg/h, 80 mg infusion followed by continuous infusion at 4 or 8 mg/h. Intragastric pH was recorded within 24 h. Plasma concentration-time curve, maximum plasma concentration (Cmax ), steady state concentration, and total plasma clearance were determined. Adverse events were also recorded.
  
  
  RESULTS
  Continuous infusion resulted in a higher mean area under the curve and Cmax than injection. There were no significant differences among the four infusion groups in terms of percentages of time at pH > 4, > 5, > 6, > 7 within 24 h and pH > 6 within the first 3 h. There were no significant differences in pharmacokinetic or pH values among variants of CYP2C19 genotype. The pH value within 24 h was unaffected by H. pylori infection in subjects with continuous infusion.
  
  
  CONCLUSIONS
  Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h.
authors.affiliation: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Jingnan
authors.initials: J
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Yang
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qian
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064098:Esomeprazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D005260:Female; D005745:Gastric Acidity Determination; D005838:Genotype; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole
keywords: esomeprazole; pharmacodynamics; pharmacokinetics; safety